Refine
Year of publication
Document Type
- Article (30440) (remove)
Language
- English (15150)
- German (13284)
- Portuguese (696)
- French (387)
- Croatian (251)
- Spanish (250)
- Italian (132)
- Turkish (113)
- Multiple languages (36)
- Latin (35)
Has Fulltext
- yes (30440)
Keywords
- Deutsch (503)
- taxonomy (420)
- Literatur (297)
- Hofmannsthal, Hugo von (185)
- Rezeption (178)
- new species (178)
- Übersetzung (163)
- Filmmusik (155)
- Johann Wolfgang von Goethe (131)
- Vormärz (113)
Institute
- Medizin (5097)
- Physik (1726)
- Extern (1108)
- Biowissenschaften (1100)
- Biochemie und Chemie (1091)
- Gesellschaftswissenschaften (798)
- Frankfurt Institute for Advanced Studies (FIAS) (696)
- Geowissenschaften (582)
- Präsidium (453)
- Philosophie (448)
Quantitative models have several advantages compared to qualitative methods for pest risk assessments (PRA). Quantitative models do not require the definition of categorical ratings and can be used to compute numerical probabilities of entry and establishment, and to quantify spread and impact. These models are powerful tools, but they include several sources of uncertainty that need to be taken into account by risk assessors and communicated to decision makers. Uncertainty analysis (UA) and sensitivity analysis (SA) are useful for analyzing uncertainty in models used in PRA, and are becoming more popular. However, these techniques should be applied with caution because several factors may influence their results. In this paper, a brief overview of methods of UA and SA are given. As well, a series of practical rules are defined that can be followed by risk assessors to improve the reliability of UA and SA results. These rules are illustrated in a case study based on the infection model of Magarey et al. (2005) where the results of UA and SA are shown to be highly dependent on the assumptions made on the probability distribution of the model inputs.
Several types of symbolic weapons are portrayed in the hands of divinities on the most diverse artistic works of the third millennium, such as maces or sceptres, daggers, spears. hows and arrows. There is also a weapon which has a form similar to a sickle. Data referring to it may be found - in addition to the representations - in written sources. We learn from the Cy1. «A» of Gudea that the king, the en-priest of Ningirsu, was the first to reach the cedar mountains and fell the cedars with his big axe. He then made the SAR.UR, the «Floodstorm Weapon» of his god, the right hand of Lagas. The inscription of statue «B» tells us the Same. When Gudea built the temple of Ningirsu, the god aided him in reaching the cedar mountains from which he took gigantic logs to make a weapon for his god: the SAR.UR, having the power ofa flood storm and the SAR.GAZ, a mace with seven copper knobs.
Background: Cyanobacteria possess several cytochrome P450s, but very little is known about their catalytic functions. CYP110 genes unique to cyanaobacteria are widely distributed in heterocyst-forming cyanobacteria including nitrogen-fixing genera Nostoc and Anabaena. We screened the biocatalytic functions of all P450s from three cyanobacterial strains of genus Nostoc or Anabaena using a series of small molecules that contain flavonoids, sesquiterpenes, low-molecular-weight drugs, and other aromatic compounds.
Results: Escherichia coli cells carrying each P450 gene that was inserted into the pRED vector, containing the RhFRed reductase domain sequence from Rhodococcus sp. NCIMB 9784 P450RhF (CYP116B2), were co-cultured with substrates and products were identified when bioconversion reactions proceeded. Consequently, CYP110E1 of Nostoc sp. strain PCC 7120, located in close proximity to the first branch point in the phylogenetic tree of the CYP110 family, was found to be promiscuous for the substrate range mediating the biotransformation of various small molecules. Naringenin and (hydroxyl) flavanones were respectively converted to apigenin and (hydroxyl) flavones, by functioning as a flavone synthase. Such an activity is reported for the first time in prokaryotic P450s. Additionally, CYP110E1 biotransformed the notable sesquiterpene zerumbone, anti-inflammatory drugs ibuprofen and flurbiprofen (methylester forms), and some aryl compounds such as 1-methoxy and 1-ethoxy naphthalene to produce hydroxylated compounds that are difficult to synthesize chemically, including novel compounds.
Conclusion: We elucidated that the CYP110E1 gene, C-terminally fused to the P450RhF RhFRed reductase domain sequence, is functionally expressed in E. coli to synthesize a robust monooxygenase, which shows promiscuous substrate specificity (affinity) for various small molecules, allowing the biosynthesis of not only flavones (from flavanones) but also a variety of hydroxyl-small molecules that may span pharmaceutical and nutraceutical industries.
Nomenclatural changes are presented for eleven species of the genus Arthothelium, resulting in four new combinations and five new synonyms. The new combinations are: Arthothelium subbessale (Nyl.) comb. nov., Cyclographina circumscissa (Vain.) comb. nov., Minksia angolensis (Nyl.) comb. nov. and Thelotrema puniceum (Müll. Arg.) comb. nov. In addition, a new species is described, Arthothelium endoaurantiacum.
Seven species of Coccocarpia are reported from the Andaman Islands and two from the Nicobar Islands. These include four species new to India and to the Andaman Islands, viz. C. glaucina, C. cf. myriocarpa, C. sp. 1 and C. sp. 2, and two species new to the Nicobar Islands, viz. C. erythroxyli and C. palmicola. A key to all nine species of Coccocarpia known from India is presented and information on morphology, chemistry and distribution given.
Elsa Triolet (1896-1970), geb. Ella Kagan, Ehefrau von Louis Aragon und Schwester von Lili Brik, war eine französische Schriftstellerin russischen Ursprungs. Ihr Werk "Roses à crédit" ("Rosen auf Kredit"), der erstes Band der Trilogie "L'âge de nylon" ("Das Nylon-Zeitalter"), schreibt sich in mehrere Gattungsformen ein. Der Verlag Gallimard bezeichnet das Werk im Untertitel der ersten Auflage von 1959 als Roman. Das für die 1994 erschienene Übersetzung ins Russische verantwortliche Verlagshaus Khorda bezeichnet ihn genauer als einen "Roman für Frauen". Mit Hilfe der von Ute Heidmann etablierten Methode des "differenzierenden Vergleichs" analysiert der vorliegende Beitrag die generischen und stilistischen Merkmale der russischen Märchen im Band "Roses à crédit". Dazu bediene ich mich seiner Übersetzung ins Russische ("Розы в кредит"), der Märchen Afanassjews, und A. Puschkins "Märchen vom Fischer und Fischlein" ("Сказка о рыбаке и рыбке"). Die vergleichende Analyse zeigt deutlich, sich das literarische Schreiben einer mehrsprachigen Autorin sich keineswegs auf eine einzige Sprache reduzieren lässt. In Elsa Triolets "Roses à crédit" lassen sich eindeutige Spuren der russischen Sprache in Form von stilistischen Merkmalen finden, die sich der Einschreibung in die Gattung der russischen Märchen verdanken.
Molecular tumour targeting has significantly improved anti-cancer protocols. Still, the addition of molecular targeting to the treatment regime has not led to a curative breakthrough. Combined mammalian target of Rapamycin (mTOR) and histone deacetylase (HDAC) inhibition has been shown not only to enhance anti-tumour potential, but also to prevent resistance development seen under mono-drug therapy. This investigation was designed to evaluate whether cross-communication exists between mTOR signalling and epigenetic events regulated by HDAC. DU-145 prostate cancer cells were treated with insulin-like growth factor (IGF) to activate the Akt-mTOR cascade or with the HDAC-inhibitor valproic acid (VPA) to induce histone H3 and H4 acetylation (aH3, aH4). Subsequently, mTOR, Rictor, Raptor, p70s6k, Akt (all: total and phosphorylated), H3 and H4 (total and acetylated) were analysed by western blotting. Both techniques revealed a link between mTOR and the epigenetic machinery. IGF activated mTOR, Rictor, Raptor, p70s6k and Akt, but also enhanced aH3 and aH4. Inversely, IGFr blockade and knock-down blocked the Akt-mTOR axis, but simultaneously diminished aH3 and aH4. VPA treatment up-regulated histone acetylation, but also activated mTOR-Akt signalling. HDAC1 and 2 knock-down revealed that the interaction with the mTOR system is initiated by histone H3 acetylation. HDAC-mTOR communication, therefore, is apparent whereby tumour-promoting (Akt/mTORhigh, aH3/aH4low) and tumour-suppressing signals (Akt/mTORlow, aH3/aH4high) are activated in parallel. Combined use of an HDAC- and mTOR inhibitor might then diminish pro-tumour effects triggered by the HDAC- (Akt/mTORhigh) or mTOR inhibitor (aH3/aH4low) alone.
The mechanistic target of rapamycin (mTOR) is elevated in prostate cancer, making this protein attractive for tumor treatment. Unfortunately, resistance towards mTOR inhibitors develops and the tumor becomes reactivated. We determined whether epigenetic modulation by the histone deacetylase (HDAC) inhibitor, valproic acid (VPA), may counteract non-responsiveness to the mTOR inhibitor, temsirolimus, in prostate cancer (PCa) cells. Prostate cancer cells, sensitive (parental) and resistant to temsirolimus, were exposed to VPA, and tumor cell growth behavior compared. Temsirolimus resistance enhanced the number of tumor cells in the G2/M-phase, correlating with elevated cell proliferation and clonal growth. The cell cycling proteins cdk1 and cyclin B, along with Akt-mTOR signaling increased, whereas p19, p21 and p27 decreased, compared to the parental cells. VPA significantly reduced cell growth and up-regulated the acetylated histones H3 and H4. Cdk1 and cyclin B decreased, as did phosphorylated mTOR and the mTOR sub-complex Raptor. The mTOR sub-member Rictor and phosphorylated Akt increased under VPA. Knockdown of cdk1, cyclin B, or Raptor led to significant cell growth reduction. HDAC inhibition through VPA counteracts temsirolimus resistance, probably by down-regulating cdk1, cyclin B and Raptor. Enhanced Rictor and Akt, however, may represent an undesired feedback loop, which should be considered when designing future therapeutic regimens.
This study was designed to investigate whether epigenetic modulation by histone deacetylase (HDAC) inhibition might circumvent resistance towards the mechanistic target of rapamycin (mTOR) inhibitor temsirolimus in a prostate cancer cell model. Parental (par) and temsirolimus-resistant (res) PC3 prostate cancer cells were exposed to the HDAC inhibitor valproic acid (VPA), and tumor cell adhesion, chemotaxis, migration, and invasion were evaluated. Temsirolimus resistance was characterized by reduced binding of PC3res cells to endothelium, immobilized collagen, and fibronectin, but increased adhesion to laminin, as compared to the parental cells. Chemotaxis, migration, and invasion of PC3res cells were enhanced following temsirolimus re-treatment. Integrin α and β receptors were significantly altered in PC3res compared to PC3par cells. VPA significantly counteracted temsirolimus resistance by down-regulating tumor cell–matrix interaction, chemotaxis, and migration. Evaluation of integrin expression in the presence of VPA revealed a significant down-regulation of integrin α5 in PC3res cells. Blocking studies demonstrated a close association between α5 expression on PC3res and chemotaxis. In this in vitro model, temsirolimus resistance drove prostate cancer cells to become highly motile, while HDAC inhibition reversed the metastatic activity. The VPA-induced inhibition of metastatic activity was accompanied by a lowered integrin α5 surface level on the tumor cells.
The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml) was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as well as tumor cell migration was examined. Effects of drug treatment on integrin α and β subtypes, on integrin-linked kinase (ILK) and total and activated focal adhesion kinase (FAK) were also determined. Integrin knock-down was carried out to evaluate integrin influence on migration and adhesion. A 24 h or 2 week amygdalin application distinctly reduced tumor cell adhesion and migration of UMUC-3 and RT112 cells. TCCSUP adhesion was also reduced, but migration was elevated under amygdalin. Integrin subtype expression was significantly and specifically altered by amygdalin depending on the cell line. ILK was moderately, and activated FAK strongly, lost in all tumor cell lines in the presence of amygdalin. Knock down of β1 integrin caused a significant decrease in both adhesion and migration of UMUC-3 cells, but a significant increase in TCCSUP adhesion. Knock down of β4 integrin caused a significant decrease in migration of RT112 cells. Since the different actions of amygdalin on the different cell lines was mirrored by β1 or β4 knock down, it is postulated that amygdalin influences adhesion and migratory properties of bladder cancer cells by modulating β1 or β4 integrin expression. The amygdalin induced increase in TCCSUP migratory behavior indicates that any anti-tumor benefits from amygdalin (seen with the other two cell lines) may depend upon the cancer cell type.